Gastroesophageal reflux disease (GORD) is a common condition induced by unwarranted reflux of gastric and duodenal contents into the esophagus, and insufficient clearance of refluxate from it. Pharmaceutical formulations possessing raft-forming capability offers an excellent alternative to conventional treatment options to treat uncomplicated GORD. These formulations typically contain a polymer, which performs distinctively upon contact with gastric acid and develops a foam-like structure that can float on gastric contents. This review aims to feature research articles and patents that cover this topic. After undergoing a standardized literature search following preferred reporting items for systematic reviews and meta-analyses guidelines, we have included 38 research articles and 18 patents describing the role of raft-forming polymers in the treatment of GORD. This is a comprehensive review of formulation/testing of raft-forming polymers. As expected, the majority of the studies focused on alginate; however, fewer studies have reported the use of pectin, xanthan gum, and raw psyllium fibers (husk). Moreover, it can be concluded from this comprehensive systematic review that a detailed characterization of raft-forming formulations, type, and concentration of used active and inactive materials and different formulations factors are essential for the development of successful anti-reflux raft-forming formulations.